In a subset of psoriasis (PsO) and psoriatic arthritis (PsA) patients, the skin and/or joint lesions appear to generate biologically significant systemic inflammation. Red cell distribution width (RDW) and mean platelet volume (MPV) are readily available clinical tests that reflect responses of the bone marrow and/or plasma thrombogenicity (e.g., inflammation), and can be markers for major adverse cardiac events (MACE). We aimed to evaluate if RDW and MPV may be employed as inexpensive, routinely obtained biomarkers in predicting myocardial infarction (MI), atrial fibrillation (AF), and chronic heart failure (CHF) in psoriatic and psoriatic arthritis patients. The study was divided into two parts: (a) case control study employing big data (Explorys) to assess MPV and RDW in psoriasis, psoriatic arthritis and control cohorts; (b) a clinical observational study to validate the predictive value of RDW and to evaluate RDW response to anti-psoriatic therapies. We used Explorys, an aggregate electronic database, to identify psoriatic patients with available MPV and RDW data and compared them to gender and age matched controls. The incidence of myocardial infarction (MI), atrial fibrillation (AF), and chronic heart failure (CHF) was highest among patients with both elevated RDW and MPV, followed by patients with high RDW and normal MPV. RDW elevation among PsA patients was associated with an increased risk of MI, AF, and CHF. In a local clinical cohort, high RDWs were concentrated in a subset of patients who also had elevated circulating resistin levels. Among a small subset of participants who were treated with various systemic and biologic therapies, and observed over a year, and in whom RDW was elevated at baseline, a sustained response to therapy was associated with a decrease in RDW. RDW and MPV, tests commonly contained within routine complete blood count (CBC), may be a cost-effective manner to identify PsO and PsA patients at increased risk of MACE.
Dysbiosis of the gut microbiome has been implicated in inflammatory bowel diseases. We have shown that levels ofCandida tropicalis, along with those ofEscherichia coliandSerratia marcescens, are significantly elevated in Crohn’s disease (CD) patients. Here, we evaluated the ability of a novel probiotic to prevent and treat polymicrobial biofilms (PMB) formed byC. tropicaliswithE. coliandS. marcescens. SinceCandida albicanshas been reported to be elevated in CD patients, we investigated the interactions ofC. albicanswith these bacterial species in biofilm formation. We determined whether the interaction betweenCandidaspp. and bacteria is specific by usingTrichosporon inkinandSaccharomyces fibuligeraas comparators. Additionally, the effects of probiotics onC. albicansgermination and biofilm formation were determined. To determine the ability of the probiotic to prevent or treat mature biofilms, probiotic filtrate was added to the PMB at early (prevention) and mature (treatment) phases. Biofilm thickness and architecture were assessed by confocal scanning laser microscopy. The effects of the probiotic on germination were evaluated in the presence of serum. Exposure ofC. tropicalisPMB to probiotic filtrate reduced biofilm matrix, decreased thickness, and inhibited hyphal formation. We showed thatC. albicansorC. tropicalisformed significantly thicker PMB than control biofilms, indicating that this interaction isCandidaspecific. Treatment with probiotic filtrate inhibitedC. albicansgermination and prevented/treatedC. albicansPMB. The designed probiotic may have utility in the management of biofilm-associated gastrointestinal diseases such as Crohn’s and colorectal cancer.IMPORTANCEThe effects of diversity of the gut microbiome on inflammation have centered mainly on bacterial flora. Recent research has implicated fungal species and their interactions with other organisms in the inflammatory process. New ways to restore microbial balance in the gut are being explored. Our goal was to identify beneficial probiotic strains that would antagonize these fungal and bacterial pathogens that are elevated in the inflamed gut, and which also have antibiofilm activity. Fungus-bacterium correlation analysis allowed us to identify candidate probiotic species that can antagonize microbial pathogens, which we subsequently incorporated into a novel probiotic formulation. Amylase, which is known to have some antibiofilm activity, was also added to the probiotic mixture. This novel probiotic may have utility for the management of inflammatory bowel diseases by disrupting polymicrobial biofilm formation.
T helper 2 (Th2) and T helper 1 (Th1) mediated immune processes lie on a spectrum. Autoeczematization secondary to chronic stasis dermatitis may fall on the Th2 side of the spectrum due to skin stretch and chronic barrier dysfunction, supporting a primary Th2 response to self-antigen. In our patient, we posited that dupilumab would benefit autoeczematization secondary to chronic stasis dermatitis given its efficacy in atopic dermatitis, a Th2-mediated immune process. We report a case of clinical psoriasiform dermatitis, suggesting a shift toward a Th1-mediated immune process developing during dupilumab treatment for autoeczematization secondary to chronic stasis dermatitis.
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